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Etiologies of nephrotic and nephritic syndrome

Nephrotic syndrome

Minimal change nephropathy

  • Accounts for most cases of nephrotic syndrome in children and 25 % of cases in adults
  • Pathophysiology: unknown, genetic association, possible circulating cytokine that results in injury to the podocytes
  • Light microscopy: normal
  • Electron microscopy: effacement of podocyte foot processes
  • Good response to high dose glucocorticoids
  • Biopsy if not responsive to treatment to exclude alternative diagnosis

Focal segmental glomerulosclerosis

  • More common in people of West African descent (due to higher carrier rates of the apolipoprotein L1 allele that is associated with FSGS)
  • Focal + segmental process = may not be evident on initial renal biopsy
    • Focal = only a certain number of glomeruli affected
    • Segmental = only parts of the glomeruli affected
      • Sclerosis may only be seen on segments of glomeruli
      • Positive staining for deposits of C3 and IgM
  • Primary FSGS
    • Severe nephrotic syndrome
    • May respond to high dose glucocorticoids
    • Immunosuppressive drugs (ciclosporin, cyclophosphamide, mycophenolate mofetil)
  • Secondary FSGS
    • Less severe nephrotic syndrome
    • Secondary to
      • HIV
      • Morbid obesity
      • Hypertension
    • Treat underlying cause

Membranous nephropathy

  • Most common cause in Caucasian patients
  • Autoantibodies directed at the surface of podocytes
  • Histology
    • Thickening of glomerular basement membrane
    • Increased matrix deposition
  • Primary membranous nephropathy
    • Idiopathic
    • High dose glucocorticoids and cyclophosphamide
  • Secondary membranous nephropathy
    • Secondary to
      • Heavy metal poisoning
      • Lupus
      • Drugs
      • Infections
      • Tumors
    • Treat underlying cause

Nephrotic and/or nephritic syndrome

Mesangiocapillary glomerulonephritis

Nephritic syndrome

IgA nephropathy

  • Most common cause of glomerulonephritis worldwide
  • Associated with minor respiratory infections
    • Within 5 days of onset after URTI
  • Histology
    • Normal serum complements
    • IgA deposits in mesangium in kidney biopsy
  • Typically progresses slowly, but in rare cases can lead to rapidly progressive glomerulonephritis (RPGN)
  • Manage with controlling blood pressure with ACEi and high dose glucocorticoids

Anti-GBM (Goodpasture’s disease)

  • Autoantibodies targeting type IV collagen which is found in both the glomerular basement membrane and the basement membranes in the lungs
    • Anti-GBM disease is when the disease is limited to the kidneys
    • Goodpasture’s disease is when the disease affects both
      • Kidneys leading to glomerulonephritis
      • Lungs leading to pulmonary haemorrhage
  • Treatment with combined plasmapheresis and glucocorticoids/immunosuppressants
  • Early diagnosis to prevent progression of renal disease

Both Wegener’s granulomatosis (now known as Granulomatosis with Polyangiitis) and Goodpasture’s disease result in combination of glomerulonephritis and pulmonary haemorrhage.

But granulomatosis with polyangiitis has more nasopharyngeal and nasal septal involvement than Goodpasture’s disease!

Post-streptococcal glomerulonephritis

  • Associated with URI – onset 10-21 days after infection
  • More common in children
  • Findings
    • Low C3 complement
    • Anti-streptococcal antibodies: elevated anti-streptolysin O and/or anti-DNase B
  • Prognosis is good, treatment is supportive
  • Antibiotics not needed as glomerulonephritis occurs after infection has subsidized