Subtypes of Idiopathic GN

Minimal Change Disease

  • Commonest cause of nephrotic syndrome in children

Aetiology

  • Idiopathic
  • Hodgkin’s lymphoma
  • Leukaemia
  • Virus

Clinical presentation

  • Facial/generalised oedema
  • Heavy proteinuria - nephrotic syndrome

Investigations

  • Normal renal biopsy on LM and IF
  • Foot process fusion on EM
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Management and prognosis

  • 94% complete remission with oral steroids
  • Some are steroid resistant or dependent, or have multiple relapses
  • Second line - cyclophosphamide, monoclonal antibodies e.g. retuximab
  • Does not cause progressive renal failure

Focal Segmental Glomerulosclerosis

  • Commonest cause of nephrotic syndrome in adults

Aetiology

  • Associated with: obesity, HIV, sickle cell, PWID, reflux nephropathy

Clinical presentation

  • Nephrotic syndrome

Investigations

  • Light microscopy - small areas of mesangial collapse and sclerosis
  • Electon microscopy:
    • Primary FSGS → diffuse podocyte process fusion
    • Secondary → podocyte process fusion limited to sclerotic areas
  • Minimal Ig/complement deposition on IF

Management and prognosis

  • Remission with prolonged steroids in 60%
  • 50% progress to end stage renal failure after 10 years
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Membranous Nephropathy

  • 2nd most common cause of nephrotic syndrome in adults

Aetiology

  • Can be primary or secondary
  • Anti PLA2r antibody is present in >70% of primary MN
  • Important secondary causes include:
    • Infections - hep. B, parasites, malaria, syphillis
    • Connective tissue diseases - SLE
    • Malignancies - lung, colon and melanoma
    • Drugs - gold/penicillamine (seen less now as not very commonly used), NSAIDs, capotropril
    • Thyroiditis

Clinical presentation

  • Nephrotic syndrome

Investigations

  • Light microscopy - thickened basement membranes, spikes on a silver stain
  • IF - granular deposits of IgG and C3 along GBM
  • EM - electron dense sub-epithelial deposits
  • Bloods - anti-phospholipase A2 antibodies

Management and prognosis

  • Rituximab used to induce remission
  • Variable, slow indolent progression
  • Less than 40% eventually develop renal failure
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Membranoproliferative

Aetiology

  • Idiopathic (type 2 has been associated with infection, SLE, malignancy)

Clinical presentation

  • Mixed nephrotic/ nephritic syndrome

Investigations

  • LM - big lobulated hypercellular glomeruli with thick membranes - tram tracks
  • IF - granular deposits of C3
  • EM - electron dense sub-endothelial deposits +/- sub-epithelial +/- mesangial

Management and prognosis

  • Depends on severity

IgA Nephropathy (Berger’s Disease)

  • Commonest form of GN in the world

Aetiology

  • Genetic
  • Acquired defect (coeliac)
  • Most commonly post-infectious e.g. URT
  • Associated with Henoch-Schonlein Purpura (HSP)

Clinical presentation

  • Nephritic - asymptomatic microhaematuria +/- non-nephrotic range proteinuria
  • Macroscopic haematuria after resp/GI infection
  • AKI/CKD

Investigations

  • LM - mesangial cell proliferation and expansion, diffuse mesangial IgA deposition
  • IF - IgA and C3 deposits in mesangium
  • EM - electron dense deposits in mesangium

Management and prognosis

  • 25% progress to end stage renal failure in 10-30 years
  • Management - BP control, ACEi and ARBs
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