nephrotic syndrome

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The nephrotic syndrome is a renal disorder characterised by heavy urinary protein losses. It is the final clinical presentation of both primary renal pathology and systemic pathologies which affect the kidney.

The nephrotic syndrome is defined by:

  • combination of heavy proteinuria (protein: creatinine ratio greater than 200 mg/mmol)
  • hypoalbuminemia (less than 25 g/L)
  • and generalized oedema
    • particularly periorbital oedema

This triad is commonly accompanied by hyperlipidaemia.

Whilst the definition appears clear, there are a number of points worth consideration:

  • with increasing age patients are more vulnerable to severe proteinurea and hypoalbuminaemia
  • the level of hypoalbuminaemia at which oedema develops varies between individuals and with age
  • other measures of renal function such as urea and creatinine, are usually normal
  • renal failure may develop
  • although the nephrotic syndrome has long thought to be due to protein loss resulting in a low albumin and low plasma oncotic pressure, patients may have a normal or increased plasma volume (this would suggest that there is not a simple relation between salt retention and renin concentration in many patients (1))

With respect to nephrotic synndrome (NS) in children:

  • approximately 80% of cases of childhood NS have minimal change disease (MCD)
  • NS is commonest glomerular disease of childhood with a median age at presentation of 4 years
  • epidemiology (3):
    • prospective studies of children with newly diagnosed idiopathic nephrotic syndrome identified through Paediatric Surveillance Units in the Netherlands, Australia and New Zealand reported incidences of idiopathic nephrotic syndrome of 1.12 to 1.9 per 100,000 children aged below 16 years
    • average incidence of nephrotic syndrome from retrospective and prospective studies to be 4.7 (range 1.15 to 16.9) per 100,000 children
    • proportion of children with steroid resistance disease varied between 2.1 to 27.3% (average 12.4%)

  • more common in males than females (ratio 3:2)
    • over 90% of cases with MCD will respond to steroid therapy, but 70% of these will develop a relapsing course
      • steroid responsiveness is the most important determining factor in the long-term prognosis of NS
    • conditions such as focal segmental glomerulosclerosis (FSGS) and mesangiocapillary glomerulosclerosis (MCGN) account for the remaining 20% of cases of NS
      • tend to present in the older child and the majority do not respond to oral steroid therapy alone
    • assumed that MCD and FSGS are immune mediated; there is controversy as to whether they are part of a spectrum or separate disorders
      • serum IgG levels are low and IgM levels are often raised
    • routine renal biopsy is not performed at presentation
      • this is because the majority of children have MCD and are likely to respond to corticosteroid

  • atypical features in a child:
    • age less than 12 months or greater than 12 years
    • persistent hypertension or impaired renal function
    • gross haematuria
    • low plasma C3
    • hepatitis B or C positive

  • childhood nephrotic syndrome is classified into steroid-sensitive nephrotic syndrome (SSNS), steroid-resistant nephrotic syndrome (SRNS), congenital and infantile nephrotic syndrome (0 to 12 months) and nephrotic syndrome secondary to other diseases including Henoch Schonlein nephritis, systemic lupus erythematosus and hepatitis B nephropathy
  • most children with primary nephrotic syndrome respond to corticosteroid therapy within four weeks (3)
  • in children who fail to respond to corticosteroids, kidney biopsy is performed to determine pathology (3)

With respect to NS in adults:

  • MCD accounts for only 10 to 25 percent of cases of nephrotic syndrome in adults
    • patients over age 16 are generally treated after kidney biopsy that shows MCD
    • initial therapy is with steroids
      • adults tend to respond more slowly, with more than 25 percent of responders taking three to four months or longer to undergo complete remission
      • approximately 50 to 75 percent of glucocorticoid-responsive adults will have a relapse, and frequent relapses occur in 10 to 25 percent
        • steroid-dependence is seen in 25 to 30 percent
    • adults with MCD are oedematous and often hypertensive
      • first-line therapy is a salt-free diet and diuretics for fluid removal
      • if antihypertensive therapy is still required, use of an angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) seems a reasonable option for blood pressure reduction, and may have the added benefit of reducing urinary protein excretion
    • there are no randomized trials to guide the optimal therapy of relapse
    • second line possible agents include cyclosporin and cyclophosphamide
      • cyclosporin combined with low dose prednisolone may be used to achieve relapse

Reference:

Last edited 07/2020 and last reviewed 08/2021

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